CYCLOADDITION-FRAGMENTATION ROUTE TO 14-BETA-ALLYLESTRONE AND THE DERIVED 14-ALPHA,17-ALPHA-ETHANO ANALOG OF ESTRIOL

3-Methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate (1) undergoes efficient baron trifluoride catalysed cycloaddition at 20 degrees C with. acrolein to give the corresponding 17 beta-acetoxy 14 alpha,17 alpha-etheno 16 alpha-carbaldebyde (2). The derived 16 alpha-tosyloxymethyl intermediates are converted via Wharton fragmentation into 14 beta-allyl derivatives of estrone. Oxidative cleavage of 14-allyl-3-methoxy-14 beta-estra-1,3,5(10)-trien-17-one (14) furnishes the 14 beta-formylmethyl derivative (17). Intramolecular reductive cyclisation of 17, followed by stepwise protection-deprotection of functionality provides an efficient synthetic route to 14,17 alpha-ethanoestra-1,3,5(10)-triene-3,16 alpha,17 beta-triol (23), the structure of which is confirmed with the aid of X-ray crystallographic analysis of the derived triacetate.